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Strategy of paramyxovirusto attenuate cytopathicity

副粘病毒减弱细胞病变性的策略

基本信息

批准号：
18590447
负责人：
TSURUDOME Masato
金额：
$ 2.57万
依托单位：
Mie University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590447/
关键词：
paramyxovirus SV5 cell-cell fusion cytopathicity multinucleated giant cell HN protein F protein receptor

项目摘要

Paramyxoviruses including simian virus 5(SV5)mediate membrane fusion through an interaction between viral envelope glycoproteins HN and F, in which the HN protein promotes fusion-inducing function of the F protein. I report here that the stalk region of SV5 HN protein is involved in the interaction with the F protein the same as those of other paramyxoviruses. Furthermore, I report for the first time that four discrete domains of the F proteins participate in the interaction with the FIN protein. As published previously, on the other hand, the T1 strain of SV5 displays reduced ability to induce cell-cell fusion and thus brings minimal cytopathicity to the virus-infected cells as compared to the prototype WR strain. To investigate the molecular mechanism of the attenuated cytopathicity of T1 virus, highly fusogenic variant was obtained from T1 virus by plaque cloning. This variant possessed three mutations L182R, K45 IT, and V536M in the FIN protein, with no mutation in the F protein. Notably, L182R mutation proved to raise the fusion-promoting function of the HN protein and that mutation of leucine at position 182 to other amino acids other than Ala also facilitates the fusion-promoting function of the HN protein. However, either of the recombinant WR viruses whose HN and/or F proteins had been replaced with the Ti counterparts were fusogenic, indicating that other T1 virus proteins such as M protein might contribute to the fusion-inhibiting function of the T1 FIN protein. Since T1 virus could perform multiple-step replication, the fusion between envelope and cell membrane seems to take place normally. We thus hypothesize that T1 FIN protein may suppresses cell-cell fusion by transducing a signal to the intracellular molecules such as actin or vinculin that the L182R mutation or combination with WR M protein may somehow cancel this suppression of signal transduction.

包括猴病毒5(SV5)在内的副粘病毒通过病毒包膜糖蛋白HN和F之间的相互作用来介导膜融合，其中HN蛋白促进F蛋白的融合诱导功能。我在此报告了SV5HN蛋白的茎区与F蛋白的相互作用，与其他副粘病毒一样。此外，我首次报道了F蛋白的四个离散结构域参与了与FIN蛋白的相互作用。另一方面，正如先前发表的那样，与原型WR株相比，SV5的T1株诱导细胞-细胞融合的能力降低，因此对感染病毒的细胞的致病作用最小。为探讨T1病毒细胞致病作用减弱的分子机制，通过空斑克隆获得了T1病毒高融合株。该突变在FIN蛋白中有L182R、K45IT和V536M三个突变，在F蛋白中没有突变。值得注意的是，L182R突变提高了HN蛋白的融合促进功能，182位亮氨酸突变为ALA以外的其他氨基酸也促进了HN蛋白的融合促进功能。然而，HN和/或F蛋白被替换为Ti蛋白的重组WR病毒中的任何一种都是融合基因，这表明其他T1病毒蛋白如M蛋白可能参与了T1 FIN蛋白的融合抑制功能。由于T1病毒可以进行多步复制，包膜和细胞膜之间的融合似乎是正常发生的。因此，我们假设T1FIN蛋白可能通过向细胞内分子如肌动蛋白或纽蛋白传递信号来抑制细胞-细胞融合，L182R突变或与WR M蛋白的结合可能以某种方式取消这种抑制信号转导的作用。

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The properties of recombinant Sendai virus having the P gene of Sendai virus pi strain derived from BEM cells persistently infected with Sendai virus

具有源自仙台病毒持续感染的BEM细胞的仙台病毒pi株P基因的重组仙台病毒的特性

DOI：
发表时间：
2006
期刊：
Medical Microbiology and Immunology 195(3)
影响因子：
0
作者：
Nishio;M.;Nagata;A.;Yamamoto;A.;Tsurudome;M.;Ito;M.;Kawano;M.;Komada;H.;Ito;Y
通讯作者：
Y

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